Humoral immune response to polyvalent pneumococcal vaccine in healthy participants receiving efgartigimod: a randomized, open-label, placebo-controlled, parallel-group phase 1 trial.

Background/objective: Efgartigimod, a human immunoglobulin G1 (IgG1) antibody Fc fragment, reduces IgG levels through neonatal Fc receptor (FcRn) blockade. Preliminary observational data suggest that efgartigimod does not impair vaccine-induced T cell-dependent antibody responses. The objective of this study was to further evaluate the effect of efgartigimod on T cell-independent humoral immune response to immunization with a 23-valent polysaccharide pneumococcal vaccine (PPSV23). Methods: In this Phase 1 open-label study, healthy adults (N=37) were randomized 1:1:1 into 3 cohorts: EFG-1 (n=12), EFG-2 (n=12), and placebo (n=13). Four weekly efgartigimod (10 mg/kg intravenously) or placebo infusions were administered with a 6-week follow-up. PPSV23 was administered immediately before (EFG-1/placebo) or 2 weeks after (EFG-2) the last efgartigimod or placebo infusion. The primary endpoint was change in pneumococcal capsular polysaccharide titers after PPSV23 vaccination. Additional endpoints included opsonizing antibody titers, antigen-specific B cell responses, and safety. Results: Although variability in antibody response was observed for individual participants and serotypes, an increase in IgG levels was observed for all 23 pneumococcal serotypes after vaccination, irrespective of efgartigimod timing. Normal response to vaccination (≥2-fold increase and >1.3 mg/L for ≥70% of serotypes) was observed in 90.0% (9 of 10) of the EFG-1 group, 54.5% (6 of 11) of the EFG-2 group, and 33.3% (4 of 12) of the placebo group. Efgartigimod did not impair production of opsonizing antibodies or antigen-specific plasma B cells. No serious/severe adverse events occurred. Conclusions: Results of this exploratory study suggest that efgartigimod has no apparent effect on T cell-independent humoral immune responses to PPSV23 vaccine in healthy adults. Participants in all groups were able to mount antigen-specific IgG responses to vaccination, even when vaccination occurred at the time of maximal reduction in total IgG. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT05163834, identifier NCT05163834.